ArticleJournal of translational medicine2020
High expression of MKK3 is associated with worse clinical outcomes in African American breast cancer patients.
Article in Journal of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.
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Who cites it
13 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Prognostic significance of the kinesin superfamily in breast cancer: A systematic review & meta-analysis.The Indian journal of medical research · 2025Pooled it
- miR-596 as a novel prognostic biomarker and tumor suppressor in breast cancer through targeting EIF5AL1.Hereditas · 2026Article
- Discriminating activating, deactivating and resistance variants in protein kinases.Genome medicine · 2025Article
- Racial Disparities in Receipt of Guideline-Concordant Care in Older Adults With Early Breast Cancer.JAMA network open · 2024Article
- Systems Pharmacodynamic Model of Combined Gemcitabine and Trabectedin in Pancreatic Cancer Cells. Part I: Effects on Signal Transduction Pathways Related to Tumor GrowthJournal of pharmaceutical sciences · 2024Article
- Landmark Series: The Cancer Genome Atlas and the Study of Breast Cancer Disparities.Annals of surgical oncology · 2023Review
- The advent of a pan-collagenous CLOVIS POINT for pathotropic targeting and cancer gene therapy, a retrospective.Frontiers in molecular medicine · 2023Review
- The Impact of Artificial Intelligence on Health Equity in Oncology: Scoping Review.Journal of medical Internet research · 2022Article
- Orthologs of human circulating miRNAs associated with hepatocellular carcinoma are elevated in mouse plasma months before tumour detection.Scientific reports · 2022Article
- Review
- A Multi-Omics Network of a Seven-Gene Prognostic Signature for Non-Small Cell Lung Cancer.International journal of molecular sciences · 2021Article
- Discovery of the first chemical tools to regulate MKK3-mediated MYC activation in cancer.Bioorganic & medicinal chemistry · 2021Article
- Immune-Omics Networks ofCancers · 2021Article
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Authors and funding
6 authors.
Funding
Abstract
backgroundAfrican American women experience a twofold higher incidence of triple-negative breast cancer (TNBC) and are 40% more likely to die from breast cancer than women of other ethnicities. However, the molecular bases for the survival disparity in breast cancer remain unclear, and no race-specific therapeutic targets have been proposed. To address this knowledge gap, we performed a systematic analysis of the relationship between gene mRNA expression and clinical outcomes determined for The Cancer Genome Atlas (TCGA) breast cancer patient cohort.
methodsThe systematic differential analysis of mRNA expression integrated with the analysis of clinical outcomes was performed for 1055 samples from the breast invasive carcinoma TCGA PanCancer cohorts. A deep learning fully-convolutional model was used to determine the association between gene expression and tumor features based on breast cancer patient histopathological images.
resultsWe found that more than 30% of all protein-coding genes are differentially expressed in White and African American breast cancer patients. We have determined a set of 32 genes whose overexpression in African American patients strongly correlates with decreased survival of African American but not White breast cancer patients. Among those genes, the overexpression of mitogen-activated protein kinase kinase 3 (MKK3) has one of the most dramatic and race-specific negative impacts on the survival of African American patients, specifically with triple-negative breast cancer. We found that MKK3 can promote the TNBC tumorigenesis in African American patients in part by activating of the epithelial-to-mesenchymal transition induced by master regulator MYC.
conclusionsThe poor clinical outcomes in African American women with breast cancer can be associated with the abnormal elevation of individual gene expression. Such genes, including those identified and prioritized in this study, could represent new targets for therapeutic intervention. A strong correlation between MKK3 overexpression, activation of its binding partner and major oncogene MYC, and worsened clinical outcomes suggests the MKK3-MYC protein-protein interaction as a new promising target to reduce racial disparity in breast cancer survival.
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